In the recent years, remarkable progress has been made in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in several promising candidates in clinical trials. However, the nano drug delivery field needs a better understanding of biological and immunological barriers, cancer pathology and immunology, and appropriate and relevant models of disease. There is a growing sentiment in the field that there is need to revisit the basics and to better understand the integrated biological, pathophysiological and immunological processes for effective translation to nanomedicine design and performance. We propose to organize a conference- workshop “Mechanisms and Barriers in Nanomedicine” in Golden, Colorado in May 2023. The program will be focused on the following aspects: a) interactions at the particle interface; b) immune recognition and toxicity of nanomaterials; c) relevance of models; d) in vivo barriers; d) new targets; d) regulatory/industrial hurdles to translation. Leading experts will discuss the integrated roles of systems immunology, protein corona, and tumor and vascular cell biology that modulate nanomedicine retention and functionality in tumors. We strive to achieve the following goals: a) to provide an educational, yet critical, forum into integrated biochemical and biological barriers controlling nanoparticle delivery and their functionality; b) to present an update and potential paradigm shift on the strategies to mitigating these problems; c) by conducting open, unrestricted, non-proprietary discussion among senior faculty, young investigators and graduate students, we hope to trigger new ideas and concepts that will move the field forward. The main innovation of the conference-workshop is in providing an open forum for discussing problems with drug delivery and in the focus on biological, immunological and translational aspects of nanotechnology. The R13 grant will be used to help with conference attendance for students and postdocs, including underrepresented, racial and ethnic groups, individuals with disabilities, individuals from disadvantaged backgrounds, and women.